Foods to avoid if you have Gout
Humans excrete approximately 0.7 g uric acid daily. Most of this is derived from the metabolic breakdown of the purine bases adenine and guanine. Uric acid is less ionized and less water soluble at most acidic pH's. It exists mostly as the monovalent salt sodium urate. However, uric acid itself may be the predominant form found in an acid urine. Because the urine becomes more acidic as it moves through the renal tubular system, filtered urate is increasingly converted to uric acid. The relatively limited solubility of urate at a urinary pH of 5 is clinically significant in patients with gout because of the possibility of the formation of uric acid stones.
While the exact mechanism of action of colchicine is unknown, the administration of the drug causes a decrease in the amount of urate crystals deposited in the various parts of the body--the result is a decrease in the inflammatory process. This drug is the oldest and most effective agent used in the treatment of acute attacks of gout. The usual dose of an acute gout attack is 1.2 milligrams immediately, then 0.6 milligram every 30 minutes to one hour until nausea and vomiting or diarrhea starts or pain is relieved. Each patient must initially titrate his own dosage. If seven tablets caused adverse effects the first administration, the patient should reduce the dosage to six tablets on the next acute attack. The usual side effect associated with the administration of colchicine is gastrointestinal irritation. Occasionally antidiarreheals are prescribed to offset this adverse effect. The patient should be informed to allow an interval of at least three days between...
NSAIDs are the preferred therapy for the treatment of acute gout. Indomethacin (Indocin), ibuprofen (Motrin), naproxen (Naprosyn), sulindac (Clinoril), piroxicam (Feldene) and ketoprofen (Orudis) are effective. More than 90 percent of patients have a resolution of the attack occurs within five to eight days. Drugs Used in the Management of Acute Gout
Lesch-Nyhan syndrome is caused by mutation in the hypoxanthine guanine phosp-horibosyltransferase (HPRT) gene on chromosome Xq26-q27.2 resulting in virtually complete deficiency of HPRT, with residual activity of less than 1.5 . Main clinical features include mental retardation, spastic cerebral palsy, extrapyramidal features with dystonia and chorea, uric acid urinary stones, and self-mutilation behavior with biting of fingers and lips 64 .
Several studies have examined the nature and prevalence of medicines prescribed for old people living in the community. One of the best known is that by Cartwright and Smith (1988) which was based on a random sample of people aged 65 and over drawn from the electoral registers of 10 parliamentary constituencies in England. Information was obtained from 78 (805 patients) of the 1032 included in the original sample. Of these 805 patients, 60 had taken one or more prescribed medicines within the preceding 24 hours. Drugs for diseases of the heart and circulation were widely prescribed and diuretics formed a therapeutic category in most widespread use. Diuretics were followed by analgesics, hypnotics, sedatives and anxiolytics drugs for rheumatism and gout and then -adrenoceptor antagonists. Similar findings were recorded in two studies from Southampton (Ridout et al, 1986 Sullivan and George, 1996). A more recent review by Jones and Poole (1998) has confirmed the rising use of...
True gastronomes have two great fears gout and a diet without salt. To guard against gout they abstain, at least occasionally, from gamey meats but against a salt-free regime they find themselves powerless and dread the doctor who prescribes it. This fear is doubly well founded. Gary Beau-champ and his colleagues at the Monell Chemical Senses Institute in Philadelphia have shown that the absence of the salt taste is not the sole inconvenience of this regime. Without salt, agreeable tastes forfeit their prominence, and they are unable to prevent disagreeable tastes from asserting themselves.
A review of laboratory tests already obtained by the primary care physician may yield important clues to the presence of an immune deficiency disorder and may save steps in the evaluation of patients by suggesting which of the more specialized tests are most likely to be informative. The complete blood count (CBC) and differential will help to exclude neutropenia or may indicate lymphopenia, which could be seen in SCID or Bruton agammaglobulinemia. Abnormal or decreased platelets may suggest Wiskott-Aldrich syndrome, and fragmented erythrocytes may suggest sickle cell disease. General blood chemistry panels will show low total protein but normal albumin in agammaglobulinemia. A low uric acid level may be indicative of ADA deficiency or purine nucleoside phosphorylase deficiency, two causes of SCID (16,38) whereas a low serum calcium level may suggest DiGeorge syndrome.
ROS relate to fat metabolism in the wound The longer-chain PuFAs are known to be more susceptible to oxidation than LC-SFA or MuFA. This susceptibility to oxidation has often led investigators to hypothesize that these fats, although essential and beneficial for many disease states, could lead to increased lipid peroxidation in tissues. An examination of the literature will find that some in vivo studies do associate dietary PuFA with increased oxidative stress.90 However, there are also many studies that indicate that dietary PuFA, especially the rn-3 fatty acids, actually decrease oxidative stress.91-94 Additional research is necessary to determine if PuFA content of cellular phospholipids and WAT at the time of wounding, or whether PuFAs supplied in the diet (oral, parenteral, enteral) are a significant factor, beneficial or otherwise, in wound oxidative stress. Because oxidative stress is known to be one of the factors capable of inducing apoptosis in cells,95-97 it could...
The toxic molybdenum dose in humans is uncertain, but it appears that the LOAEL dose is about 1.6 mg kg and the NOAEL dose about 0.9 mg kg in rats. The human equivalent of these is about 26 and 15 milligrams per day, respectively. A dose of 26 milligrams per day is much higher than the 0.2 to 0.5 milligram per day dose commonly prescribed in noncancerous conditions. At high doses, side effects of molybdenum can include aching joints resembling gout, headache, anemia, and adverse effects on fetal development. Anemia and fetal impacts, which were seen in rodents, may be largely caused by low plasma copper concentrations low copper concentrations can produce iron deficiency and inhibit the angiogenesis needed for fetal development.
Discourse concerning hysterical and hypochondriacal distempers. In Dr. Sydenham's complete method of curing almost all diseases and descriptions of their symptoms. To which are now added five discourses of the same author concerning pleurisy, gout, hysterical passion, dropsy and rheumatism (3rd edn), p. 149. Newman and Parker, London.
Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine.
N Engl J Med 1996 334 445-451. Gonzalex EB, Miller SB, and Agudelo CaA. Optimal management of gout in older patients. Drug Ther 1994 4 128-134. Grantham JJ and Chonko AM. Renal handling of organic anions and cations Excretion of uric acid. In Brenner BM and Rector FC (eds.). The Kidney (4th ed.). Philadelphia Saunders, 1991. Schlesinger N and Schumacher HR Jr. Gout Can management be improved Curr Opin Rheumatol 2001 13 240-244. Taylor CT, Brooks NC, and Kelley KW. Corticotropin for acute management of gout. Ann Pharmacother 2001 35 365-368. Star VL and Hochberg MC. Prevention and management of gout. Drugs 1993 45 212-222. Terkeltaub RA. Gout and mechanisms of crystal-induced inflammation. Curr Opin Rheumatol 1993 5 510-516.
The differential diagnosis includes granulomatous and giant cell lesions of the heart. Granulomatous infections are uncommon in immunocompetent patients, but we routinely perform histochemical stains for fungal and mycobacterial microorganisms. In general, necrotizing granulomas are found in infectious lesions. Giant cell myocarditis is characterized by the presence of giant cells but, by definition, granulomas are absent. In hypersensitivity myocarditis, the histiocytic lesions are poorly formed and are centered on collagen fibers. Eosinophils are numerous, but multinucleated giant cells and fibrosis are not found. The granuloma-like lesions of acute rheumatic fever are poorly formed, and the giant cells are generally smaller and do not resemble Langerhans type. Foreign body-type giant cells surrounding catheter sheath fragments can be found in biopsy specimens of patients undergoing repeated biopsy procedures (Fig. 14-5 A). The edge of healing ischemic infarcts can contain giant...
Patients with chronic renal failure usually become symptomatic when glomerular filtration rate is less than 10 ml min. Uraemia affects every organ system, including the central nervous system. There may be arrhythmias, anorexia, nausea, vomiting, anion gap acidosis, hypocalcaemia, fluid overload, hyperlipidaemia, hyperparathyroidism, increased insulin resistance, pruritus, anaemia, bleeding disorders, pulmonary oedema, pneumonitis, pleuritis, gout, and muscle weakness. Neuropsychiatric manifestations of chronic renal failure include irritability, insomnia, lethargy, anorexia, seizures, and restless legs syndrome. (89 In contrast to acute renal failure where neuropsychiatric signs and symptoms may appear with a creatinine level as low as 4 mg dl in chronic renal failure, patients may have a normal mental status examination with a serum creatinine level as high as 10 to 11 mg dl. Symptomatic treatments with low-dose neuroleptics, antiseizure medications, or
Molybdenum is an essential trace element that is ubiquitous in the environment and vital in plant and animal biochemistry. In human nutrition Mo is assimilated primarily from vegetables. It is closely associated with copper and iron metabolism and enzymatic redox processes involving an equilibrium between the Mo6+, Mo5+, and Mo4+ forms, e.g., in the oxidation of aldehydes, sulfites and nitrates, and of molecular nitrogen (1). In plants, the so-called MoFe protein, a component of nitrogenase, is essential for nitrogen fixation (2). Toxic levels of molybdenum are rarely attained, as the metal is rapidly eliminated renally from mammalian organisms. In humans, gout, characterized by high levels of uric acid excretion, is more prevalent in regions with high Mo concentrations in agricultural soil and plants (3). High levels of exposure to Mo as the mineral dust occur in the foundry industry and in molybdenum ore mining.
The use of the shock of the torpedo, an electric fish, for the treatment of gout was described by Aetius, a Greek physician, more than 1000 years ago (14). In 1747, Veratti enunciated the concept of applying an electric current to increase the penetration of drugs into surface tissues (15). In 1898, Morton demonstrated that finely powdered graphite could be driven into his arm under the positive electrode and produced small black spots that persisted for weeks (16). In 1900, Leduc reported the first controlled studies of iontophoresis as a therapeutic modality (17,18). Leduc showed that transcutaneous iontophoretic delivery of strychnine and cyanide ions into rabbits produced fatal tetanic seizures and cyanide poisoning.
Renal transplantation is associated with several functional and structural abnormalities of the skeletal system. Some of these complications such as persistent hyperparathyroidism, aluminum-associated bone disease, B-2 microglobulin amyloidosis may be preexistent at the time of transplantation. Subsequent development of osteopenia, osteonecrosis and gout may cause additional skeletal problems. The most common posttransplant skeletal disorders are immunosuppression related bone disease, painful leg syndrome and avascular bone necrosis.
The dehydrogenase (XD) oxidizes hypoxanthine to yield uric acid and is coupled with a reduction of NAD into NADH. Once the enzyme is converted to the oxidase form (XO), the same reaction utilizes molecular oxygen as an electron acceptor and serves as a superoxide-generating system. Endothelial cells in microvessels, but less those in larger vessels, serve as a major source of the XD XO system. In the mesentery, where the vasculature constitutes a major source of the enzyme, both XD + XO and XO activities are elevated in SHR compared to WKY rats (Suzuki et al., 1998).
Form, exists as a homodimer of two protein molecules. Catalysis occurs by transfer of electrons along a chain of molybdo-pterin cofactor, two Fe2S2 sites, and an FAD site. XOR can be the target of oxidation and proteolysis, modifications that change the binding specificity of the enzyme and lead to the formation of xanthine oxidase (XO). Unlike XDH, which binds to NAD+ as its preferred electron acceptor leading to the formation of NADH, XO can no longer bind NAD+. However, the enzyme XO retains its activity in the conversion of hypoxanthine into xanthine and uric acid, and utilizes molecular oxygen as an electron acceptor, leading to the formation of the highly reactive oxygen species superoxide. The alteration in binding specificity for NAD+ is irreversible in the case of proteolysis, but can be reversed by reducing agents in the case of oxidation. However, it is important to point out that the dehydrogenase form of XOR can also utilize molecular oxygen and produce ROS, albeit less...
Patients classically present with enlarged liver and subsequent preprandial hypoglycemia and may manifest acute hypoglycemia with intercurrent illness or fast. Lactic acidosis from the chronic energy depletion state provides a source of energy for the brain, and often the hypoglycemia goes unnoticed until an illness occurs. Long-term sequelae can include liver adenomas, progressive renal insufficiency, and gout.
Labs CBC, platelets, SMA 7&12, creatinine, BUN, potassium, magnesium, phosphate, calcium, uric acid, osmolality, ESR, INR PTT, ANA. Urine specific gravity, UA with micro, urine C&S 1st AM spot urine electrolytes, creatinine, pH, osmolality Wright's stain, urine electrophoresis. 24h urine protein, creatinine, sodium.
Increases tubular flow and is most useful in rhab-domyolysis, hemolysis, uric acid nephropathy, and dysfunction resulting from contrast and other nephrotoxic agents. Most effective if given before toxic event. Use with care in oliguric states, because if drug is not excreted, it will increase hyper-osmolarity and volume overload of renal failure.
I send a very imperfect answer to your question, which I have written on foreign paper to save you copying, and you can send when you write to Thomson in Calcutta. Hereafter I shall be able to answer better your question about qualities induced in individuals being inherited gout in man--loss of wool in sheep (which begins in the first generation and takes two or three to complete) probably obesity (for it is rare with poor) probably obesity and early maturity in short-horn cattle, etc., etc.
Uric acid Uric acid (UA) is the naturally occurring product of purine metabolism, and it is known as a strong peroxynitrite scavenger (a product of nitric oxide and superoxide radicals). Hooper et al. (74,75) demonstrated that the inhibition of iNOS or scavenging of NO* or peroxynitrite by UA inhibited neurological deficits in mice with EAE, while withdrawal of iNOS inhibitor resulted in the appearance of neurological signs within 24 h (74,75).
Scientists have tried to explain this evolutionary dilemma (118-123), which has been comprehensively reviewed by Benzie (117). It could shift the average population age down to enhance fertility, protect against hemolytic glucose-6-phosphate dehydrogenase deficiency in areas where malaria is endemic, accelerate evolution via increased exposure of DNA to ROS, and enhance the efficacy of our early immune response. These hypotheses are unlikely, however, and the best explanation probably resides in positive selection for an inactivation of the L-gulono-lactone oxidase gene, perhaps in a staged downregulation. This would fit into a paradigm of optimizing metabolic efficiency by using dietary sources of vitamin C, which exist in abundance. The metabolic cost of manufacturing vitamin C de novo might then, over the course of time, be diverted to a more pressing biochemical process. This argument is strengthened by the fact that noxious hydrogen peroxide is produced as part of vitamin C...
In 1731, the physician and botanist Jacobus Theodorus Tabernaemontanus reported in a collection of herbal remedies that mistletoe never touching the ground is used for childhood epilepsy, when applied as a pulverised drug, or even by wearing it as a silver-amulet. Mistletoe was also applied for deworming children, to treat labour-pains, gout, and affections of lung and liver (Tabernaemontanus, 1731). However, when applied in wine, mistletoe was used to treat leprosy. When applied as a plaster, mistletoe was suggested to be beneficial in the treatment of mumps and fractures, while the binding of their leaves to the palms and sole will heal hepatitis (Tabernaemontanus, 1731).
Agnogenic myeloid metaplasia-myelofibrosis has been described by at least 37 different names, such as idiopathic myelofibrosis with myeloid metaplasia.124,125 Patients with this entity generally present with anemia, massive splenomegaly, and nucleated and tear-drop red cell forms in the peripheral blood. Basophilia and an elevation of the white count with a left shift are not uncommon although as the disease progresses, leukopenia may supervene.126 Early in the disease (before marrow fibrosis occurs) the marrow may be simply hypercellular and the disease unclassifiable. The platelet count may be high, normal, or decreased. Serum B12 and B12 binding proteins tend to be elevated as is the uric acid level, each suggestive of a significant degree of cell turnover.
In vitro antagonism between nitrofurantoin and the quinolones has been shown, but a demonstration of clinical relevance warrants further study. Certain drugs used in treating gout, which inhibit tubular secretion, can affect UTI therapy by raising serum levels of nitro-furantoin with concomitant diminished urinary levels.
The thiazides have a variable effect on elimination of uric acid, which also is secreted by the renal acid secretory mechanism. Administration of thiazide diuretics, especially at low doses, may elevate serum uric acid levels and cause goutlike symptoms. Following large doses, thiazides may compete with uric acid for active reabsorption and thereby may promote uric acid elimination rather than impair it (see Chapter 37).
Hydroxymethylglutaryl coenzyme-A (HMGCoA) reductase inhibitors, better known as statins, are the most potent lipid-lowering agents, consistently documented to prevent or reduce cardiovascular events in primary and secondary prevention (168-170). The therapeutic potential of this type of drug is probably far greater than previously anticipated (171). Many of the nonlipid lowering effects of statins could be of major relevance to a variety of disease processes. For example, statins enhance nitric oxide production and improve endothelial function, display anti-inflammatory potency, inhibit integrins, and lower circulating adhesion molecules (172,173). As with statins, fibrates have also been shown to reduce coronary risk (LOCAT study) the beneficial nonlipid effects with respect to atherosclerotic prevention include antithrombotic effects (decrease in fibrinogen and PAI1), anti-inflammatory activity (inhibition of TNF-a-induced endothelial expression of VCAM-1 and IL6), and decrease in...
The inhibitory effects of tea polyphenols on xanthine oxidase (XO) were investigated.43 Catechins and theaflavins inhibit XO to produce uric acid and also act as scavengers of superoxide. The antioxidative activity of tea catechins is due not only to their ability to scavenge superoxides, but also to their ability to block XO and related oxidative signal transducers.43 It has been demonstrated that tea or tea catechins inhibit Cu2+-mediated LDL oxidation in vitro44 and induction of atherogenesis in mice.39 To determine whether tea catechins act as effective antioxidants in vivo, future studies in animals and humans should employ sensitive and specific biomarkers of oxidative damage to DNA, proteins, and lipids.
Pathogenesis of the abnormalities and clinical syndromes that make up the IRS. To begin with, type 2 diabetes is the only clinical syndrome listed in Table 3 that is not associated with a significant degree of hyperinsulinemia. Obviously, in this instance, it is the failure of the pancreatic P-cell to adequately compensate for the insulin resistance that is responsible for the development of the clinical syndrome 16 . In the case of the other abnormalities and clinical syndromes listed in Tables 2 and 3, it is the relationship between insulin resistance, compensatory hyperinsulinemia, and the individual tissue response to the chronically elevated plasma insulin concentrations that is responsible for the observed pathophysiology. In this context, it is necessary to address the question of differential tissue insulin sensitivity, for if this phenomenon did not exist, there would be no IRS. For example, the ability of insulin to stimulate muscle glucose uptake and inhibit free fatty acid...
The enzyme urate oxidase has also found medical application for the treatment of acute hype-ruricaemia (elevated plasma uric acid levels), associated with various tumours, particularly during their treatment with chemotherapy. Uric acid is the end-product of purine metabolism in humans, other primates, birds and reptiles. It is produced in the liver by the oxidation of xanthine and hypoxanthine (Figure 12.16), and is excreted via the kidneys. Owing to its relatively low solubility, an increase in serum uric acid levels often triggers the formation and precipitation of uric acid crystals, typically resulting in conditions such as gout or urate stones in the urinary tract. Significantly elevated serum uric acid concentrations can also be associated with rapidly proliferating cancers or, in particular, with onset of chemotherapy. In the former instance, rapid cellular turnover results in increased rates of nucleic acid catabolism and, hence, uric acid production. In the latter case,...
Older patients with long-standing alcoholism are at high risk for development or aggravation of many medical problems, especially liver disease, several cancers, disorders of glucose, fat and uric acid metabolism, osteoporosis, anaemias, congestive heart failure, aspiration pneumonia, and accidental injuries. (7) Control of hypertension and diabetes mellitus is compromised by heavy drinking. Acute doses of alcohol compete with many medications (e.g. warfarin, phenytoin, most benzodiazepines, propanolol) for hepatic drug metabolizing enzymes in the cytochrome P-450 system, which can produce higher than desired drug blood levels, while chronic alcohol dosing induces the cytochrome P-450 system and can lead to more rapid metabolism of the same medications, with resulting lower than desired drug blood levels.(8) Inhibition of hepatic alcohol dehydrogenase by such drugs as chlorpromazine and isoniazid, or inhibition of gastric alcohol dehydrogenase by histamine receptor antagonists (e.g....
Beta-blockers interfere with the absorption of epinephrine, leading to decreases of heart rate and blood pressure, although caffeine, alcohol, and salt can reverse the effects.8 Furthermore, an increase of triglycerides may result from the use of beta-blockers.33,34 Diuretics may impair lipid profile, cause glucose intolerance, and result in elevation of uric acid.33 Resperpine and methyldopa are also used in some parts of the world. Aspirin is used as an antiplatelet therapy.23
Patients with PV are often plethoric and may complain of pruritus, which is classically related to bathing or showering in warm water (aquagenic pruritus) and may be intractable. They may also describe headaches and blurred vision, night sweats, and gout, attributable to hyperviscosity, hypervolemia, and hypermetabolism. Splenomegaly is present in around two-thirds of PV patients at diagnosis and its prevalence increases with disease duration.17 However, in most cases the diagnosis of PV is first suspected following an abnormal full blood count performed to investigate nonspecific or unrelated symptoms.
(2) Measurement of dietary antioxidants in vivo. These methods generally measure the concentration in plasma, whole blood, or tissues, of enzymes that contribute to the antioxidant defense or of several antioxidants. Such methods include measurement of enzymes such as superoxide dismutase (SOD), catalase, and glutathione reductase (GTr) (95). Other methods include the determination of tocopherols, vitamin C, carotenoids, some polyphenols, uric acid, and others (96,97). However, more recent studies also demonstrated ROS participation in signaling pathways and in communicating important information to the cell's genome in a carefully regulated manner (126-129). These studies demonstrated that hypoxia during sleep leads to ATP depletion followed by an increase in purine catabolic products, namely adenosine and uric acid. Since the production of uric acid during reoxygenation is accompanied by free radical production, these findings indirectly suggest that increased oxidative stress does...
Peroxynitrite's relevance in biochemistry was first noted by Beckman et al. (1990) and Radi et al. (1991) and during the next ten years evidence of the formation of this oxidant in vivo accumulated. Initially considered a toxic species, peroxynitrite, like H2O2 (Rhee, 2006), has recently started to be regarded as potentially involved in redox signaling pathways (Bachschmid, et al., 2005 Touyz, 2005). By 2000, the mechanisms that control peroxynitrite toxicity and possible signaling functions remained unclear It was known that the reaction with carbon dioxide represented one important pathway of decay, but this reaction represented only a diversion of reactivity from peroxynitrite to carbonate radical (CO3-), which also is an oxidizing species, and therefore cannot be regarded as a true detoxification pathway. Analogous considerations applied for the fast reactions between peroxynitrite and some heme proteins (Table 3), except for the case of oxyhemoglobin that isomerizes peroxynitrite...
One of the chief concerns regarding the consumption of microorganisms as a protein source is their high concentration ofnucleic acid, primarily RNA. Yeast and bacteria contain approximately three to eight times as much RNA per gram as does meat. High levels of nucleic acid in the diet cause an increase in uric acid in the blood, which can lead to gout and kidney stones. Chemical and enzymatic methods are being developed to decrease the nucleic acid in SCP without altering the nutritional value of the protein.
Direct examination of MS plaques revealed increased free radical activity. Moreover, along with the increased ROS, decreased levels of several antioxidants, including glutathione, alpha-tocopherol, and uric acid, was found (60). Furthermore, Vladimirova et al. (61) found oxidative damage to DNA in plaques of MS brains induced by activated mononuclear cells. They also found higher production of ROS in mononuclear cells of MS patients, compared with controls (62). These elevated ROS and nitric oxide levels led to oxidative damage to DNA, including mitochondrial DNA, in association with inflammation in chronic active plaques (63).
The fact that uric acid, the end product of XOR catalysis in humans, is a strong antioxidant also raised speculation about the importance of XOR catalysis as an antioxidant rather than a pro-oxidant system. However, XOR continues to be a formidable generator of ROS when exogenously added to cultured cells. In vivo, XOR-derived ROS may be sufficient to directly damage cells, or to combine with NO (in the case of superoxide) in endothelial cells to produce highly reactive and damaging species such as peroxynitrite. Alternatively, XOR-derived ROS may be operative as signaling molecules mediating specific cellular responses to stress, such as interaction of phagocytes with endothelial cells. A recent review suggested an evolutionarily conserved role for XOR in innate immunity 3 . Microvascular endothelial cells or mammary and intestinal epithelial cells are proposed to protect the organism through production of the antioxidant uric acid. Furthermore, signaling through XO-derived ROS may...
Additional evaluation may be of aid in the diagnosis of acute uremia. Severe hypocalcemia at the onset of oliguria occurs in rhabdomyolysis and pancreatitis. Very high levels of uric acid accompany tumor lysis, trauma, or muscle damage. Eosinophilia is frequent in acute interstitial nephritis. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are characterized by hemolytic anemia, thrombocytopenia, and the presence of schistocytes, and disseminated intravascular coagulation is characterized by anemia, thrombocytopenia, and prolonged prothrombin, partial thromboplastin, and thrombin times associated with low fibrinogen titers and elevated levels of fibrin degradation products.
Ascorbic acid, vitamin E, lipoic acid, uric acid, bilirubin, and b-carotene are among a group of endogenous free radical scavengers. The antioxidant action of these compounds is due to their ability to donate an electron to an oxidant species, thereby inactivating it. Because transition metals such as iron and copper can react with O2- to form the highly reactive hydroxyl radical (Off), another group of compounds that act as metal chelators also contribute to antioxidant defenses. These compounds include ferritin, ceruloplasmin, and transferrin.
A major driving force for this increased activity was the work of Gabrial Andral. Recognizing the value of chemical analysis of body fluids, he argued effectively for increased research by the medical community (5,6). He was a believer in chemical and microscopic examination of the liquid as well as the solid components of the body (5,6). His work, Pathological Hematology, examined blood chemically, microscopically, and visually in both the healthy and diseased populations (6). He measured or calculated the major components of blood and was able to demonstrate a decreased red cell mass in anemia and a decreased blood albumin in albuminuria (6). The success of Andral's work coupled with his enthusiasm led other workers to pursue similar investigations. The studies of sugar in the blood of diabetics and uric acid in the blood of those who suffered from gout are prime examples of this effort (5).
The binding of uric acid to plasma proteins is relatively small and probably does not have great physiological significance. However, even this limited binding may be affected by administration of drugs, such as salicylates, phenylbutazone, probenecid, and sulfinpyrazone. These drugs probably affect urate protein binding only secondarily that is, their principal action is to interfere with renal transport of uric acid, which in turn leads to alterations in plasma urate binding. The renal mechanisms involved in the handling of uric acid are complex and involve filtration, reabsorption, secretion, and possibly postsecretory reabsorption. The proximal tubule is the principal site of both carrier-mediated reabsorption and secretion of urate. Urate is believed to be transported from the ultrafiltrate to the intracellular space by an anion (hydroxyl, bicarbonate, chloride, or lactate) exchange mechanism in the luminal membrane. This active transport system can be inhibited by drugs, such as...
A fairly large number of structurally-related compounds give a positive murexide reaction. They are useful as an identification reaction for uric acid (Figure 3.34.5) and other purine derivates. These substances all contain the same structural feature as the six-membered heterocyclic ring of xanthine.
Phenylbutazone (Butazolidin) is metabolized to oxy-phenbutazone (Phlogistol), and both compounds have all of the activities associated with the NSAIDs. Their use is accompanied by serious adverse reactions, such as anemia, nephritis, renal failure or necrosis, and liver damage. Because of their toxicity, they are prescribed only for the treatment of pain associated with gout or phlebitis or as a last resort for other painful inflammatory diseases resistant to newer and less toxic treatments. Interactions with a large number of other drugs
Some substances filtered at the glomerulus are reabsorbed by active transport systems found primarily in the proximal tubules. Active reabsorption is particularly important for endogenous substances, such as ions, glucose, and amino acids (Fig. 4.4), although a small number of drugs also may be actively reabsorbed. The probable location of the active transport system is on the luminal side of the proximal cell membrane. Bidirectional active transport across the proximal tubule also occurs for some compounds that is, a drug may be both actively reabsorbed and secreted. The occurrence of such bidirectional active transport mechanisms across the proximal tubule has been described for several organic anions, including the naturally occurring uric acid (see Chapter 37). The major portion of filtered urate is probably reabsorbed, whereas that eventually found in the urine is mostly derived from active tubular secretion. Most drugs act by reducing active transport rather than by enhancing...
As with adults, the primary organ responsible for drug metabolism in children is the liver. Although the cy-tochrome P450 system is fully developed at birth, it functions more slowly than in adults. Phase I oxidation reactions and demethylation enzyme systems are significantly reduced at birth. However, the reductive enzyme systems approach adult levels and the methylation pathways are enhanced at birth. This often contributes to the production of different metabolites in newborns from those in adults. For example, newborns metabolize approximately 30 of theophylline to caffeine rather than to uric acid derivatives, as occurs in adults. While most phase I enzymes have reached adult levels by 6 months of age, alcohol dehydrogenase activity appears around 2 months of age and approaches adult levels only by age 5 years.
Large doses cause a flushing of the skin as a result of the dilation of blood vessels but the effect is not harmful. A form of niacin, niacinamide, does not cause any skin sensations, however, large doses can damage the liver and cause depression in some people. The form inositol hexanicotinate lowers serum cholesterol without harming the liver. Doses of the vitamin should not exceed 1000 mg a day, unless under the supervision of a physician. High doses of niacin should not be taken during pregnancy, or in cases of ulcers, gout, diabetes, gallbladder or liver diseases, or recent heart attack.
Side effects of nicotinic acid include flushing, pruritus, gastrointestinal discomfort, hyperuricemia, gout, elevated liver function tests and glucose intolerance. Taking 325 mg of aspirin 30 minutes before the drug is ingested may minimize flushing. Therapy should be avoided in diabetes mellitus because it tends to worsen glycemic control.
Several studies have confirmed the high incidence of ADRs in elderly patients taking antihypertensives. For example, on a geriatric ward de V Mering noted severe cough induced by captopril, enalapril-induced angioedema and bronchospasm, peripheral vascular symptoms caused by ,3-adre-noceptor blockers and gout precipitated by thia-zides (de V Mering, 1991). In the community, 3.1 of respondents reported an ADR with propranolol, 2.5 with methyldopa and 2.2 with nifedipine (Chrischilles et al., 1992a). For patients admitted to geriatric wards, antihyperten-sive drugs were a frequent cause of ADRs leading to hospital admissions (Hallas et al., 1992). The fl-adrenoceptor blockers were a particularly common cause, and in some patients had been prescribed despite contraindications (Gosney and Tallis, 1984 Lindley et al., 1992).
Figure 1 Uric acid stones (A) CT SPR image obtained at 80 kVp and 300mA reveals no opaque renal stones. A large calcified gallstone (arrow) projects over the right-upper quadrant of the abdomen. (B) Unenhanced CT scans demonstrate a 2 cm stone in the right renal pelvis and a tiny caliceal tip renal stone. (C) Renal pelvic stone appears as a filling defect (arrow) on the bone window setting of the pyelographic phase image of a subsequently performed enhanced CT. (D) CT SPR image obtained eight minutes after intravenous contrast administration shows the large uric acid stone as a filling defect (large arrow) in the right renal pelvis (calcified gallstone, small arrow). Abbreviations CT, computed tomography SPR, scanned projection radiography. Figure 1 Uric acid stones (A) CT SPR image obtained at 80 kVp and 300mA reveals no opaque renal stones. A large calcified gallstone (arrow) projects over the right-upper quadrant of the abdomen. (B) Unenhanced CT scans demonstrate a 2 cm stone in...
The consistent findings of decreased levels of the major antioxidant glutathione in the substantia nigra of patients with idiopathic PD has provided the basis for the oxidative stress hypothesis of the etiology of this neuro-degenerative disease. Recent studies have explored whether the nigral glutathione deficiency seen in idio-pathic PD is present in patients with parkinsonism associated with nigral damage (PSP and MSA). These studies reveal decreased nigral levels of reduced glutathione in postmortem brain of patients with PD and PSP. A similar decrease was seen in the MSA patient group, but this did not reach statistical significance. Levels of reduced glu-tathione were within normal limits in all unaffected brain regions and in degenerating extranigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (anti-oxidant and product of purine catabolism) also was observed in nigra of all patient groups (-19 to -30 ). These data suggest that glutathione depletion,...
The glomerular filtrate initially enters the proximal tubule of the nephron where an estimated two-thirds of it is isosmotically reabsorbed, coupled with the active transport of sodium. Proximal sodium reabsoption is chiefly an active process, relying on Na +,K+-ATPase pumps. The primary anions of the extracellular fluid, choride and bicarbonate, accompany sodium reabsorption via a Na+ H+ countertransport exchange system in order to maintain electrical neutrality. Bicarbonate, glucose, and amino acids (cotransported with sodium) are almost complete reabsorbed in the proximal tubule. This nephron segment, displaying a high permeability to water, also links volume and solute reabsorption. The rate of ionic and water proximal tubule reabsorption is invariably subject to the kidney's interpretation and regulation of the body's physiological requirements. Finally, the proximal tubule is a major site of creatinine and organic acid (uric acid) secretion. Physical factors modulating proximal...
Another significant feature of the proximal tubule is that it is the site of organic acid transport. This is important in understanding both the pharmacokinetics of many of the diuretics, most of which are weak organic acids, and also certain of the side effects induced by these drugs. For instance, uric acid, which is the end product of purine metabolism in humans, is both reabsorbed and secreted by the organic acid transport pathway (see Chapter 37).
Tubular backleak plays a minor role in mild or non-oliguric forms of toxic or ischemic ARF. As the severity of renal ischemia increases, the contribution of tubular wall permeability to the suppression of glomerular filtration is enhanced. Immunoglobulin light-chain cast precipitation may complicate plasma cell dyscrasias and intraluminal pigments may play a role in rhabdomyolysis and hemoglobinuria, although the correlation between cast deposition and renal failure is weak. Tubular dilatation may be seen with intratubular precipitation of crystals (uric acid, oxalate, acyclovir, methotrexate, sulfonamides), as typically seen in the tumor lysis syndrome
Contrast nephropathy more often afflicts those patients with combined risk factors, particularly prior renal dysfunction, diabetes mellitus, and volume depletion. Suggested pathogenetic mechanisms of contrast-induced ARF include direct tubular cell toxicity, intraluminal precipitation of proteinaceous casts or uric acid crystals,
Uric acid may be actively reabsorbed from the ultrafiltrate following its glomerular filtration or it may be secreted from the blood across the basolateral membrane into the proximal tubular cell. Both passive and active transport mechanisms are involved in the handling of urate. Uricosuric drugs at appropriate doses interfere with these processes.
Didanosine should be used with great caution in individuals who have a history of pancreatitis. Didanosine tablets contain phenylalanine and should not be taken by phenylketonurics. Didanosine should be used cautiously in patients with gout, peripheral neuropathy, and advanced AIDS.
Busulfan is used in the palliative treatment of chronic granulocytic leukemia. Daily oral therapy results in decreased peripheral white blood cells and improved symptoms in almost all patients during the chronic phase of the disease. Excessive uric acid production from rapid tumor cell lysis should be prevented by coadministration of allopurinol.
Increase the dosage to 500 mg bid after 1 week, then increase by 500-mg increments every 4 weeks until the uric acid level is below 6.5 mg dL. Max dose 2 g d. Contraindicated during acute attack. 10. Labs CBC, SMA 7, uric acid. UA with micro. Synovial fluid for light and X-ray views of joint. 24 hour urine for uric acid.
Staghorn calculi are most commonly composed of struvite and are associated with recurrent urinary tract infections. Complete stone removal is essential in these patients because failure to do so allows persistence of infection and the eventual regrowth of the stone (Fig. 2). Other stones that may occasionally have a staghorn configuration are cystine stones, uric acid stones, and, rarely, calcium oxalate monohydrate stones. Staghorn calculi can range in size from a surface area that is less than 250 mm2 to greater than 5000 mm2 (200).
The uricosuric drugs (or urate diuretics) are anions that are somewhat similar to urate in structure therefore, they can compete with uric acid for transport sites. Small doses of uricosuric agents will actually decrease the total excretion of urate by inhibiting its tubular secretion. The quantitative importance of the secretory mechanism is relatively minor, however, and at high dosages these same drugs increase uric acid elimination by inhibiting its proximal tubular reabsorption. Thus, uricosuric drugs have a seemingly paradoxical effect on both serum and urinary uric acid levels at low doses, they increase serum levels while decreasing the urinary levels they have the opposite effect on these two levels at high dosages. The two most clinically important uricosuric drugs, probenecid and sulfinpyrazone, are organic acids. The initial phase of therapy with uricosuric drugs is the most dangerous period. Until uricosuric drug levels build up sufficiently to fully inhibit uric acid...
Sulfinpyrazone, although less effective than allop-urinol in reducing serum uric acid levels, remains useful for the prevention or reduction of the joint changes and tophus deposition that would otherwise occur in chronic gout it has no antiinflammatory properties. During the initial period of sulfinpyrazone use, acute attacks of gout may increase in frequency and severity. It is recommended, therefore, that either colchicine or a nonsteroidal antiinflammatory agent be coadministered during early sulfinpyrazone therapy.
Osteoporosis may be akin to a silent thief. As it evolves, the patient has no symptoms and is not aware of the developing disease. Routine blood work-up including sedimentation rate, complete blood count, creatinine, calcium, phosphorus, uric acid, liver function tests, thyroid stimulating hormone, parathyroid hormone, alkaline phospha-tase, and serum vitamin D levels remain normal throughout. Frequently the disease is diagnosed late when the patient sustains a spontaneous vertebral fracture or breaks a long bone following minimal trauma. Fractures tend to occur in the vertebral bodies, proximal hip, distal radius, and proximal humerus. Vertebral fractures are a major source of morbidity and affect the quality of life of many patients. There are approximately 700,000 new vertebral fractures each year in the United States. These fractures may be incidentally discovered in films obtained for other reasons and are frequently missed by inexperienced physicians.
When osteoporosis or vertebral fractures are detected, systemic diseases such as hematological malignancies (multiple myeloma or metastatic disease) should be excluded. The work-up should include sedimentation rate, complete blood count, serum calcium, phosphorus, uric acid, serum and urine protein electrophoresis, and liver function tests. Osteoporosis work-up should also include blood levels of 25-hydroxyvitamin D, parathyroid hormone, osteocalcin (a bone formation marker), and 24-hour urine calcium excretion.
This X-linked recessive condition, which almost exclusively affects boys, was first described in 1964 by William Nyhan. (24) Although often described as a rare condition, the incidence rate quoted for this condition varies widely between 1 in 10 000 and 1 in 380 000 live births. The usual mode of inheritance is from a carrier mother to her affected son. The syndrome is caused by an inborn error of purine metabolism, resulting in an abnormally high level of xanthine and uric acid in the blood of the affected person. A deficient production of hypoxanthine phosphoriposyl transferase is responsible for the abnormality in purine metabolism. The gene locus for hypoxanthine phosphoriposyl transferase has recently been identified in the short arm of chromosome Xq26-27.
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